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Rani et al., J Blood Disorders Transf 2013, 5:2

http://dx.doi.org/10.4172/2155-9864.1000192

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Variable Manifestations of Severe Hypoprothrombinemia (Factor II

Deficiency): 2 Cases
Sirisha Rani S*, Darshak Makadia, Lokesh Lingappa, Nikit Shah and Ramesh Konanki
Department of Hematology Oncology, Department of Paediatric Neurology, Rainbow Childrens Hospital and Perinatal Centre, Hyderabad, India

Abstract
Case 1 is a 28 months female child, who has been symptomatic from 8 month of age with multiple, painful
bruises over legs once in 5 to 6 weeks. Her complete blood picture was normal.PT and APTT were prolonged
with normal fibrinogen and liver function.
Case 2, became symptomatic from day 2 of life. He was treated for blood stained vomiting and black coloured
stool and severe anaemia. Second episode was subdural hemorrhage and seizures. Investigations revealed
abnormal PT and APTT with normal fibrinogen and liver function. Hereditary prothrombin deficiency is one of the
rare congenital coagulation defect encountered in clinical practice. High index of suspicion is required to diagnose
this condition with systematic approach as the facility to check factor 2 levels are not freely available in many
centres. Bleeding manifestations are dependent on factor level. Children with severe deficiency are prone for
life threatening bleeds. We report couple of children who had severe form of hereditary prothrombin deficiency
with variable clinical manifestations. In both the cases, coagulation profile was suggestive of common pathway
defect, PT and APTT were prolonged. Fibrinogen and Liver function tests were normal. No evidence of sepsis, no
response to vitamin K. Further evaluation revealed low prothrombin activity (<1%). Factor v and x were normal.

Keywords: Hypoprothrombinemia; Prothrombin; Thromboplastin;

Hemorrhage

increase factor II levels before surgery. Prothrombin complex concentrates

either for treatment or prophylaxis are also recommended [6,7].

Introduction

Case 1

Prothrombin (factor 2) is a precursor to thrombin, which converts

fibrinogen into fibrin, which in turn strengthens protective clot [1].
Deficiency of this factor results in impaired clotting mechanism and
manifests as prolonged bleeding. There are two types of prothrombin
deficiencies, hereditary and acquired. Hereditary prothrombin
deficiency is an autosomal recessive inheritance rare congenital coagulation
disorder with a prevalence of approximately 1:2,000,000 in the general
population and nearly 100 cases are reported worldwide [1,2].

A 28 months old girl, symptomatic from 8-months of age, born to

second degree consanguineous couple, second in birth order presented
with complaints of painful bruises over lower limbs, disturbed sleep at
nights with pain. Her elder sibling was a male child, who also suffered
from similar problem, died at the age of two years with bleeding.
Diagnosis was not established.

Hereditary hypoprothrobinemia can be either Type I prothrombin

deficiency (hypoprothrombinemia) or Type II prothrombin deficiency
(dysprothrombinemia).
Severity of clinical features varies from easy bruisability to severe
intracranial hemorrhage and hematoma. It depends on prothrombin
activity, patients with prothrombin activity of 5-50% usually bleed
following trauma and surgery, while those with prothrombin activity
of 2-5%, bleeding is variable and those with activity <1%, present with
significant bleeding tendency [1-3].
Diagnosis is suspected with a prolonged prothrombin time (PT) and
an activated partial thromboplastin time (APTT); definite diagnosis is
through specific factor assay.
Acquired form of hypoprothrombinemia could be secondary
to vitamin K deficiency, liver disease or autoimmune disorders like
SLE. Oral anticoagulant therapy also can create acquired form of
hypoprothrombinemia status [4,5]. In Systemic Lupus Erythematosus
(SLE) hypoprothrombinemia is secondary to inhibitors to prothrombin.
Studies of family members, checking ANA titres and measurement of
vitamin K dependent coagulation factors helps to distinguish acquired
from inherited prothombin deficiency [1,2].
Simple bruises and mild superficial bleeding do not generally
require therapy. Infusion of fresh frozen plasma (FFP) is adequate in
most cases of bleeding. Plasma exchange transfusion may be used to
J Blood Disorders Transf
ISSN: 2155-9864 JBDT, an open access journal

Investigation of our patient had done elsewhere revealed prolonged

PT and APTT.
Patients complete blood counts (platelets 2.7 lakhs) and peripheral
blood smear were normal. Both PT and APTT were more than 2 mts,
which was getting corrected with normal plasma in mixing studies.
Other investigations such as fibrinogen, liver function test, septic
markers and bleeding time did not reveal any abnormality. There was
no response to vitamin K. ANA was normal. Prothrombin activity was
less than 1%. She was transfused with fresh frozen plasma as per the
need. Patient is now 28 months and she is thriving well. For recurrent
painful bruises disturbing night sleep with pain, she is requiring FFP
every 5-6 weeks, which resolves her symptoms.

*Corresponding author: Sirisha Rani S, Department of Hematology Oncology,

Department of Paediatric Neurology, Rainbow Childrens Hospital and Perinatal
Centre, Hyderabad, India, Tel: 09959985558; E-mail: lokisiri@gmail.com
Received December 06, 2013; Accepted December 27, 2013; Published
December 31, 2013
Citation: Sirisha Rani S, Makadia D, Lingappa L, Shah N, Konanki R (2013)
Variable Manifestations of Severe Hypoprothrombinemia (Factor II Deficiency):
2 Cases. J Blood Disorders Transf 5: 192. doi: 10.4172/2155-9864.1000192
Copyright: 2013 Sirisha Rani S, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.

Volume 5 Issue 2 1000192

Citation: Sirisha Rani S, Makadia D, Lingappa L, Shah N, Konanki R (2013) Variable Manifestations of Severe Hypoprothrombinemia (Factor II
Deficiency): 2 Cases. J Blood Disorders Transf 5: 192. doi: 10.4172/2155-9864.1000192

Page 2 of 2

Case 2
A 12 days old baby boy second child of third degree consanguineous
couple, admitted with complaint of blood stained vomiting and
black coloured stool at local hospital. He received vitamin K and
FFP transfusion for coagulopathy (PT and APTT were prolonged)
in local hospital. He was not investigated further at that time. No
history of similar complaints in the family. On day 40 of life he had
persistent vomiting and tonic posturing of the body. His CT brain
revealed subdural hemorrhage. He had low hb of 7 gm%, platelets
were 3.5 lakhs/cu mm, PT was 51seconds and APTT 87 seconds. His
prothrombin activity was less than 1%. Fibrinogen, septic markers and
LFT were normal. He required ventilator support, packed red blood cell
(PRBC) transfusion, vitamin K and fresh frozen plasma (FFP). He was
discharged after 7 days. At 2 and half months of age, he developed left
ankle swelling secondary to bleed. He received FFP transfusion. At 3
months of age he came with irritability and excessive crying. His repeat
CT brain revealed sub dural, sub arachnoid and intra parenchymal
bleed with cystic encephalomalasia changes (Figures 1 and 2). He
received same treatment.
He is now 6 months old, parents were counselled regarding nature
of the condition, probable need of frequent transfusion. Also explained
about possible poor neurological outcome secondary to extensive CNS
bleed.
In both the patients there was no icterus, lymphadenopathy and
visceromegaly. Their anthropometry was normal. In both the cases,
common pathway defect was suspected on the basis of prolonged PT
and APTT. There was no response to vitamin K. No evidence of sepsis
or liver disease. Clotting factors assay including fibrinogen, factor V
and factor X were normal. ANA was negative. Both had prothrombin
activity <1%. Both the parents had normal PT and APTT. Their
prothrombin activity was not done (Table 1).

Discussion
Patients with inherited severe hypoprothrombinaemia present
early in life, whereas a patient with milder form may present later at
any age. Severe life-threatening haemorrhage, including intracranial
haemorrhage [6], is found in neonates with severe prothrombin
deficiency and prophylactic therapy is recommended for them. Severe
prothrombin deficiency leads to spontaneous abortion and foetal
demise in some cases. Complete prothrombin deficiency has not been

PT
Case 1

APTT

More than
More than 2 mts
2 mts

Case 2

51

87

Fibrinogen
and LFT

ANA

Factor 2
activity

normal

normal

Less than 1%

normal

normal

Less than 1%

Table 1: As quantitative assement of factor 2 by immunological assay is not freely

available, in our cases factor 2 activities has been done which was less than 1%
in both the cases.

reported; suggesting that this condition is incompatible with life. In

both acquired and inherited hypoprothrombinaemia, the morbidity
and mortality risks are related to the circulating level of factor II [2].
Prophylactic treatment is suggested in children with severe deficiency
(levels less than 2%) with life threatening bleeds [6,7].
Despite having very low (<1%) prothrombin level in both patients,
case 1 girl had only subcutaneous bruises requiring FFP occasionally
when symptomatic with painful bruises disturbing sleep. She is not on
prophylactic treatment. Currently she is 28 months old and thriving
well. Where as second child had recurrent intra cranial bleeds in early
infancy and carries poor prognosis.
Moderate bleeding can be treated with Fresh Frozen Plasma.
Correction of prothrombin can also be achieved with the use of
Prothrombin complex concentrates (PCCs) [3,8]. PCCs contain
factors II, VII, IX and X. However, there are differences in the amount
of factor II present in PCCs, depending upon the product. The major
disadvantage of PCCs is a potential for thrombosis, presumably because
of contamination of factors such as FXa and FIXa. The dose of infused
product should not exceed 100 units/kg, and the frequency of infusion
should be adjusted to maintain hemostasis but not excessive level of
prothrombin.
References
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Figures 1 and 2: Bilateral subdural bleed, acute on chronic on right & left
parenchymal bleed with exvacua dilatation.

J Blood Disorders Transf

ISSN: 2155-9864 JBDT, an open access journal

Citation: Sirisha Rani S, Makadia D, Lingappa L, Shah N, Konanki R

(2013) Variable Manifestations of Severe Hypoprothrombinemia (Factor II
Deficiency): 2 Cases. J Blood Disorders Transf 5: 192. doi: 10.4172/21559864.1000192

Volume 5 Issue 2 1000192